Living Donor Whole and Partial Liver Grafts, Deceased Donor Whole Liver and SPLIT: Outcome Comparison.

BACKGROUND: Currently, graft options for pediatric liver transplantation (PLT) include whole (WL) and partial (P) grafts, in the form of either deceased donor transplantation (DD) or living donor liver transplantation (LD). WL transplants from LD are commonly referred to as domino LT. The objective of this manuscript is to compare the outcomes of PLT performed with each of the available graft options. METHODS: Retrospective cohort study from Jan. 2010 to Dec. 2022. The variables included data on the recipients' preoperative clinical status, intraoperative technical aspects, post-operative complications, and survival studies. There were 4 groups: SPLIT (17), DD-WL (55), LD-WL (824), and LD-P (22). RESULTS: The median age and BW of the recipients was smaller in SPLIT, LD-P, and LD-WL compared to DDT-WL groups. HVOO (HR 15.87, 95% CI 1.89-133.06, P = 0.01), retransplantation (HR 7.94, 95% CI 2.63-24.02, P < 0.01), and malignancies (HR 3.08, 95% CI 1.29-7.37, P = 0.01) were independently associated with decreased patient survival. HAT (HR 27.54, 95% CI 10.44-72.68, P < 0.01) and malignancies (HR 2.42, 95% CI 1.10-5.34, P = 0.03) increased the risk of graft loss. The overall survival in this series was 91.4% (mean follow-up of 74.3 months). Patient and graft survival were not different among groups. CONCLUSION: HAT and malignancies were associated with reduced graft survival. Whole liver from living donors with MSUD presented 100% patient survival at 120 months. Even without statistical differences in survival among the studied groups, LD-P and LD-WL recipients presented a trend towards better outcomes. LEVEL OF EVIDENCE: LEVEL III.

Living Donor Liver Transplantation as a Backup Procedure: Treatment Strategy for Hepatocellular Adenomas Requiring Complex Resections.

METHODS: We present a series of three patients with large hepatocellular adenoma lesions showing a central location, for which the living donor liver transplantation strategy was used as a backup procedure. RESULTS: Hepatocellular adenoma was confirmed by biopsy in all patients. Surgical resection was indicated because of the patients' symptoms and lesion size and growth. All patients had a lesion that was central or in close contact with major vessels. The final decision to proceed with the resection was made intraoperatively. A live donor was prepared for all three patients. Two patients underwent portal vein embolization associated with extended hepatectomy, and a total hepatectomy plus liver transplantation with a living donor was performed in one patient. All patients had good postoperative outcomes. CONCLUSIONS: In the treatment of hepatocellular adenomas for which complex resections are necessary and resectability can only be confirmed intraoperatively, surgical safety can be improved through the use of a living donor backup. Center expertise with living donor liver transplantation is paramount for the success of this approach.

Perioperative blood transfusion decreases long-term survival in pediatric living donor liver transplantation.

BACKGROUND: The impact of perioperative blood transfusion on short- and long-term outcomes in pediatric living donor liver transplantation (PLDLT) must still be ascertained, mainly among young children. Clinical and surgical postoperative complications related to perioperative blood transfusion are well described up to three months after adult liver transplantation. AIM: To determine whether transfusion is associated with early and late postoperative complications and mortality in small patients undergoing PLDLT. METHODS: We evaluated the effects of perioperative transfusion on postoperative complications in recipients up to 20 kg of body weight, submitted to PLDLT. A total of 240 patients were retrospectively allocated into two groups according to postoperative complications: Minor complications (n = 109) and major complications (n = 131). Multiple logistic regression analysis identified the volume of perioperative packed red blood cells (RBC) transfusion as the only independent risk factor for major postoperative complications. The receiver operating characteristic curve was drawn to identify the optimal volume of the perioperative RBC transfusion related to the presence of major postoperative complications, defining a cutoff point of 27.5 mL/kg. Subsequently, patients were reallocated to a low-volume transfusion group (LTr; n = 103, RBC ≤ 27.5 mL/kg) and a high-volume transfusion group (HTr; n = 137, RBC > 27.5 mL/kg) so that the outcome could be analyzed. RESULTS: High-volume transfusion was associated with an increased number of major complications and mortality during hospitalization up to a 10-year follow-up period. During a short-term period, the HTr showed an increase in major infectious, cardiovascular, respiratory, and bleeding complications, with a decrease in rejection complications compared to the LTr. Over a long-term period, the HTr showed an increase in major infectious, cardiovascular, respiratory, and minor neoplastic complications, with a decrease in rejection complications. Additionally, Cox hazard regression found that high-volume RBC transfusion increased the mortality risk by 3.031-fold compared to low-volume transfusion. The Kaplan-Meier survival curves of the studied groups were compared using log-rank tests and the analysis showed significantly decreased graft survival, but with no impact in patient survival related to major complications. On the other hand, there was a significant decrease in both graft and patient survival, with high-volume RBC transfusion. CONCLUSION: Transfusion of RBC volume higher than 27.5 mL/kg during the perioperative period is associated with a significant increase in short- and long-term postoperative morbidity and mortality after PLDLT.

Domino Liver Transplant in Maple Syrup Urine Disease: Technical Details of Cases in Which the First Surgery Involved a Living Donor.

BACKGROUND: Data describing the technical aspects of living donor (LD) domino liver transplantation (DLT) in maple syrup urine disease (MSUD) are limited. The largest published series includes only 3 cases. One great challenge of this procedure is to ensure adequate vascular stumps for the LD, the MSUD patient, and the recipient of the domino graft. Here, we describe our experience in 11 cases of LD-DLT in MSUD, highlighting the technical aspects of LD-DLT. METHODS: From September 2012 to September 2017, 11 patients with MSUD underwent LD liver transplantation at our institution, and MSUD livers were used as domino grafts in 11 children. RESULTS: (1) MSUD patients: 10 patients received a left lateral segment. The donor's left hepatic vein (HV) was anastomosed to the confluence of the recipient's 3 HVs. No vascular grafts (VG) were required for portal vein (PV) anastomosis. Single arterial anastomosis was performed with microsurgery in 10 of 11 patients. (2) MSUD graft recipients: In 8 cases, HV reconstruction was performed between the graft's HV confluence and the recipient's HV confluence, and in 3 cases, a vena cava triangulation was necessary; 6 MSUD grafts required HV venoplasty. No VG were needed for HV reconstruction. VG were used for PV reconstruction in 3 cases due to sclerotic PV. In 2 cases, double arterial anastomoses were performed in the MSUD liver. All patients remain alive and well. CONCLUSIONS: Living donor liver transplantation followed by DLT for MSUD is a complex procedure and demands technical refinement. Special attention must be paid to vascular reconstruction.

Outcomes of liver transplantation in pediatric recipients with cardiovascular disease.

LT exerts considerable stress on the heart perioperatively. Limited data exist on impact of cardiovascular diseases on LT children. This study evaluated the outcomes of children with CVD who underwent LT and compared with pretransplant findings. From 518 LT recipients, 82 (15.8%) had CVD. Sixty patients were classified as low-risk adjustment for congenital heart surgery 1 (RACHS 1 and 2). Five patients were classified as RACHS ≥3. The most common echocardiographic finding in the CVD patients (25/82) was ASD. CVD patients had more abnormal EKG (32.4% vs 14.5%, P < .001), abnormal chest X-ray (11.8% vs 1.4%, P < .001), and altered echocardiography (89.7% vs 15.4%, P < .001) findings compared with the No-CVD group pretransplant. Post-transplant, significant differences between groups were observed related to abnormal EKG (14.7% vs 7.0%, P = .03) and echocardiography (48.5% vs 3.2%, P < .01) findings. Pretransplant ASD spontaneously closed in 22 patients. At 1 and 5 years post-transplant, there was no difference in the survival rate between groups (P = .96). The prevalence of CVD in recipients of LT was high, and its presence was associated with significantly higher cardiac decompensation before and after LT. Minor and moderate cardiovascular disease did not impact the long-term survival.

Pediatric Liver Transplant: Techniques and Complications.

Liver transplant is considered to be the last-resort treatment approach for pediatric patients with end-stage liver disease. Despite the remarkable advance in survival rates, liver transplant remains an intricate surgery with significant morbidity and mortality. Early diagnosis of complications is crucial for patient survival but is challenging given the lack of specificity in clinical presentation. Knowledge of the liver and vascular anatomy of the donor and the recipient or recipients before surgery is also important to avoid complications. In this framework, radiologists play a pivotal role on the multidisciplinary team in both pre- and postoperative scenarios by providing a road map to guide the surgery and by assisting in diagnosis of complications. The most common complications after liver transplant are (a) vascular, including the hepatic artery, portal vein, hepatic veins, and inferior vena cava; (b) biliary; (c) parenchymal; (d) perihepatic; and (e) neoplastic. The authors review surgical techniques, the role of each imaging modality, normal posttransplant imaging features, types of complications after liver transplant, and information required in the radiology report that is critical to patient care. They present an algorithm for an imaging approach for pediatric patients after liver transplant and describe key points that should be included in radiologic reports in the pre- and postoperative settings. Online supplemental material is available for this article. ©RSNA, 2017.

Analysis of Factors Associated With Biliary Complications in Children After Liver Transplantation.

BACKGROUND: Biliary complications (BCs) remain an important cause of morbidity after pediatric liver transplantation. Technical factors have already been implicated in the development of BCs. Previous reports have associated the use of partial grafts, particularly living donor grafts, with a higher incidence of BCs. Our aim is to study the factors associated with the development of BCs in a large cohort of pediatric liver transplant recipients. METHODS: Retrospective cohort study of 670 children (<18 years of age) who underwent a primary liver transplant between March 2000 and January 2015. Patients who did and did not develop BCs were compared with identify associated factors. Univariate and multivariate analyses were performed. RESULTS: A total of 115 patients (17.2%) developed BCs (83 strictures and 44 leaks). Of the study participants, 594 had living donor liver transplants. Multiple arterial anastomoses was a protective factor for BCs, and a ductoplasty was a risk factor. Living donor grafts and multiple biliary anastomoses were more frequently associated with leaks. Patients with BCs had a higher reoperation rate and longer hospital stays. There was no difference in patient or graft survival. CONCLUSIONS: Technical factors play a major role in the development of BCs, particularly leaks. Strictures are more frequently associated with an inadequate arterial supply to the bile duct, and multiple arterial anastomoses may protect children from this complication. The use of partial grafts was not an independent factor for BCs in high-volume centers that are experienced with this technique.

Simultaneous or sequential gastrectomy in pediatric liver transplant recipients.

The association between LT and gastrectomy is not common. Only two studies reported the gastrectomy/LT association in children. Here, we report three children who underwent LT who required a concomitant or sequential gastrectomy for different reasons. Patient 1, a 16-yr-old boy, during the LT, underwent a partial gastrectomy due to extensive injury to the duodenum. He had a previous and unusual portoenterostomy performed in the duodenum. Bowel reconstruction was performed using an intestinal loop that was first used for the bilio-enteric anastomosis and then connected to the gastric stump. Patient 2, a 22-month-old female child, underwent a partial gastrectomy with a Roux-en-Y reconstruction during a retransplantation. She had a large perforated gastric ulcer blocked by the allograft liver. Patient 3, a 26-month-old male child, five yr after living donor LT, was submitted to a partial gastrectomy because of gastric outlet obstruction. The histopathology was compatible with eosinophilic gastritis. The association between LT and gastrectomy in the pediatric population is extremely rare. Appropriate knowledge of the previous transplantation technique is very important. Further studies are required to assess the outcomes of the different types of gastric reconstruction in pediatric recipients.

Outcomes and technical aspects of liver retransplantation with living donors in children.

Re-LT is the only recourse for patients with liver graft failure. However, survival rates after re-LT are lower than those of primary transplants. Few reports are available regarding re-LT with LDs in children. The objective of this study was to describe our cohort of patients retransplanted with LD and emphasize the technical aspects of a re-LT with LD. This is a retrospective report of a series of 18 children (<18 yr old) submitted to 20 re-LT from January 1997 to December 2013 at Hospital Sirio-Libanes and Hospital AC Camargo Cancer Center. The one- and five-yr survival for patients retransplanted with LD was 70.6% and 58.6%. Little technical modifications from a regular LD primary transplant were needed in patients retransplanted with LD. Seven (38.8%) patients presented vascular complications following re-LT and three presented biliary complications (16.6%). In conclusion, a re-LT with LD is an acceptable alternative for children who experience liver graft failure and it does not compromise the donor pool. Further experience with re-LT with LD may support this therapy.

Twenty Years of Experience in Pediatric Living Donor Liver Transplantation: Focus on Hepatic Artery Reconstruction, Complications, and Outcomes.

BACKGROUND: Hepatic artery thrombosis (HAT) increases morbidity and mortality after liver transplantation (LT). The identification of risk factors for HAT may aid transplant teams in the development of strategies aimed at reducing HAT. This article describes the risk factors for HAT and outcomes after LT. METHODS: This report describes a retrospective study (1995 to 2015) of primary pediatric living donor LT (LDLT). Pretransplant and technical variables were included in the study. Binary logistic regression was used for data analysis. RESULTS: This study included 656 primary LDLT. The median age, body weight, and pediatric end-stage liver disease score at the time of transplant were 13 months, 8.4 kg and 15, respectively. Twenty-one (3.2%) patients developed HAT. Intraoperative HAT (odds ratio, 62.63; 95% confidence interval, 12.64-310.19; P < 0.001) and the use of liver grafts with a graft-to-recipient weight ratio less than 1.1% (odds ratio, 24.46; 95% confidence interval, 4.55-131.56; P < 0.001) retained statistical significance in the multivariate model. Patient and graft survivals were significantly worse in cases with HAT. The overtime trend analysis revealed a decrease in the incidence of HAT (P = 0.008) and an increase in the use of 2-arterial anastomosis (P < 0.001). CONCLUSIONS: A graft-to-recipient weight ratio of 1.1% or less and intraoperative HAT were independently associated with HAT. Trend analysis further revealed a significant reduction in the incidence of HAT over time, as well as the increased use of 2 hepatic arteries for anastomosis during graft implantation. The double artery anastomosis may represent an extra protection to pediatric recipients undergoing LDLT.

Biliary complications after pediatric liver transplantation: Risk factors, diagnosis and management.

The expanded indications of partial grafts in pediatric liver transplantation have reduced waiting list mortality. However, a higher morbidity is observed, including an increased rate of biliary complications (BCs). Factors such as the type of graft, the preservation methods applied, the donor characteristics, the type of biliary reconstruction, and the number of bile ducts in the liver graft influences the occurrence of these complications. Bile leaks and strictures comprise the majority of post-transplant BCs. Biliary strictures require a high grade of suspicion, and because most children have a bileo-enteric anastomosis, its diagnosis and management rely on percutaneous hepatic cholangiography and percutaneous biliary interventions (PBI). The success rates with PBI range from 70% to 90%. Surgery is reserved for patients who have failed PBI. BCs in children after liver transplantation have a prolonged treatment and are associated with a longer length of stay and higher hospital costs. However, with early diagnosis and aggressive treatment, patient and graft survival are not significantly compromised.

HCC prevalence and histopathological findings in liver explants of patients with hereditary tyrosinemia type 1.

BACKGROUND: Untreated tyrosinemia type 1 (HT1) is manifested by liver failure associated with renal tubular dysfunction, growth failure, and rickets. The indication for liver transplantation (LT) is restricted to non-responders to 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) treatment, patients not treated with NTBC or for patients with HCC. The aim of this study is to report on a series of NTBC naive HT1 patients submitted to LT along with the prevalence of HCC in their liver explants. PROCEDURE: This is a retrospective study of 16 children with HT1 who underwent liver transplantation between January 1993 and December 2012. CLINICAL FEATURES: liver failure in 12 (75%), growth failure in 4 (25%), rickets in 5 (31.2%), hypertrophic cardiomyopathy in three (18.7%), and renal tubulopathy in seven patients (43.7%). Median AFP level was 64,335 ng/ml. Abdominal CT scans showed multiple nodules in most patients. Histopathology of the explants showed cirrhosis in all patients and HCC in 12 (75%), 3 with microvascular invasion. The majority of the tumors were well differentiated. Patient survival rate was 86% at a median follow-up of 6.6 years. All survivors were tumor-free with no adjuvant chemotherapy. CONCLUSION: In countries where neonatal screening programs are not effective and NTBC treatment is not widely available, LT still plays an important role in the treatment of children with HT1. An early indication in patients who present with multinodular livers can also serve to treat an otherwise underdiagnosed HCC condition.

Diagnosis and management of biliary complications in pediatric living donor liver transplant recipients.

The incidence of biliary complications (BCs) after living donor liver transplantation (LDLT) can reach 40%. Published data on the pediatric population are limited, and treatment protocols vary. Our aim was to describe the clinical scenario for BCs and treatment approaches after LDLT. Between October 1995 and December 2012, 489 pediatric LDLT procedures were performed. BCs developed in 71 patients (14.5%). Biliary strictures (BSs) developed in 45 (9.2%) patients, and bile leaks (BLs) developed in 33 patients (6.7%). The BL diagnosis was clinical in all cases, and 69.7% of the patients underwent surgery. Nearly half of the BS cases had clinical features or suggestive ultrasound findings. Liver biopsy findings suggested BSs in 51.7%. Percutaneous transhepatic cholangiography was performed in 95.6% of the BS patients. The success rate was 77% [mean number of percutaneous biliary interventions (PBIs) = 3.9 ± 1.98, median drainage time = 8 months]. In conclusion, BL patients can be managed with conservative therapy, even though most of these patients will ultimately be treated with surgery. Diagnosing a BS requires a high degree of clinical suspicion because the available resources for its identification can fail in up to 50% of cases. A higher number of PBIs and the use of a drainage catheter for a longer time may be required to achieve better results with this technique.

Low-dose carbon monoxide inhibits progressive chronic allograft nephropathy and restores renal allograft function.

Chronic allograft nephropathy (CAN) represents progressive deterioration of renal allograft function with fibroinflammatory changes. CAN, recently reclassified as interstitial fibrosis (IF) and tubular atrophy (TA) with no known specific etiology, is a major cause of late renal allograft loss and remains a significant deleterious factor of successful renal transplantation. Carbon monoxide (CO), an effector byproduct of heme oxygenase pathway, is known to have potent anti-inflammatory and antifibrotic functions. We hypothesized that inhaled CO would inhibit fibroinflammatory process of CAN and restore renal allograft function, even when the treatment was initiated after CAN was established. Lewis rat kidney grafts were orthotopically transplanted into binephrectomized allogenic Brown Norway rats under brief tacrolimus (0.5 mg/kg im, days 0-6). At day 60, CO (20 ppm) inhalation was initiated to recipients and continued until day 150 or animal death. Development of CAN was confirmed at day 60 with decreased creatinine clearance (CCr), significant proteinuria, and histopathological findings of TA, IF, and intimal arteritis. Air-treated control recipients continued to deteriorate with further declines of CCr and increases of urinary protein excretion and died with a median survival of 82 days. In contrast, progression of CAN was decelerated when recipients received CO on days 60-150, showing markedly improved graft histopathology, restored renal function, and improved recipient survival to a median of >150 days. CO significantly reduced intragraft mRNA levels for IFN-gamma and TNF-alpha at day 90. Expression of profibrotic TGF-beta/Smad was significantly suppressed with CO, together with downregulation of ERK-MAPK pathways. Continuous CO (20 ppm) treatment for days 0-30, days 30-60, or days 0-90, or daily 1-h CO (250 ppm) treatment for days 0-90, also showed efficacy in inhibiting CAN. The study demonstrates that CO is able to inhibit progression of fibroinflammatory process of CAN, restore renal allograft function, and improve survival even when the treatment is started after CAN is diagnosed.

Left lateral segmentectomy for pediatric live-donor liver transplantation: special attention to segment IV complications.

BACKGROUND: During left lateral segmentectomy for live-donor liver transplant, the vascular inflow to segment IV can be compromised. An area of ischemia can be seen intraoperatively and further segment IV resection may be needed to prevent necrosis and abscess formation. METHODS: From July 1995 to February 2007, 324 consecutive living donor liver transplantations were performed at Hospital A. C. Camargo and Hospital Sirio-Libanes, Sao Paulo, Brazil. Two hundred eleven left lateral segments were transplanted in this period. Data on 204 left lateral segments donors were available for this analysis. RESULTS: There were 108 female and 96 male donors. Median age was 29 years (range, 16-48 years). Median follow-up time was 2.2 years (range, 2 months-11.8 years). Median intensive care unit stay was 1 day (range, 1-3 days), and median hospital stay was 5 days (range, 4-47 days). Postoperative complications were encountered in 39 donors (19.1%). Partial segment IV resection on the course of the primary surgery due to parenchyma discoloration was required in 107 cases (52.5%). Ten patients (4.9%) developed segment IV necrosis or abscesses, although four of them had had segment IVB resection intraoperatively. Segment IV necrosis or abscess significantly increased hospital stay and the number of readmissions, from 5.5+/-3.5 days to 8.4+/-3.7 days (P=0.012) and from 6 of 194 (3%) to 5 of 10 (50%) (P=0.001), respectively. CONCLUSIONS: Middle hepatic segment abscess or necrosis was the most frequent complication after left lateral segmentectomy (4.9%). Objective intraoperative strategies need to be developed to evaluate middle hepatic segment ischemia to identify and treat patients at higher risk.

Gastric hemangioma in a 5-year-old boy.

We report a rare cause of gastrointestinal bleeding in a 5-year-old boy with hematemesis and melena for a month. Upper gastrointestinal endoscopy and an abdominal magnetic resonance image suggested a large hemangioma on the gastric fundus. The patient underwent an exploratory laparotomy with partial gastrectomy limited to the gastric fundus. An intraoperative endoscopy helped to ensure a complete resection of the tumor. Histopathology showed a cavernous hemangioma of the gastric fundus.

Carcinoma of donor origin after liver-intestine transplantation in a child.

Tumor-related complications after intestinal transplantation in children have been principally EBV driven post-transplant disorders. We describe the clinical course of a child, with a diagnosis of microvillus inclusion disease who received a liver and intestine allograft at the age of 9 months. His postoperative course was significant for multiple episodes of acute intestinal allograft rejection and eventually the development of post-transplant lymphoproliferative disorder (PTLD), which resolved. At 8 yr post-transplant he presented with masses in the intestine allograft mesentery and in the right lobe of the allograft liver, biopsy of which revealed a relatively undifferentiated tumor, suggestive of a carcinoma. In situ hybridization for X and Y chromosomes, revealed his tumor to be of donor origin. Treatment included debulking of the mesenteric mass with segmental enterectomy of the intestinal allograft, and stopping his immunosuppression for a period of 4 months; this resulted in complete resolution of his malignancy. Immunosuppression with tacrolimus and steroids was restarted because of intestinal allograft rejection; he died suddenly of unknown causes at 17 months post-diagnosis of carcinoma. The severely immunosuppressed state produced in this patient allowed for the development of an unusual donor derived carcinoma, which resolved spontaneously with withdrawal of immunosuppression. The mechanism of such regression of tumor may be related to restitution of immunologic competence, but is yet to be determined.

Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts.

BACKGROUND: Heme oxygenase (HO)-1 system has been shown to provide protection against oxidative stress through the degradation of heme to biliverdin, free iron, and carbon monoxide (CO). This study investigated cytoprotective efficacy of CO at a low concentration on cold ischemia/reperfusion (I/R) injury of transplanted intestine. METHODS: Lewis rat recipients of syngenic orthotopic small intestinal transplantation with 6 hours UW cold preservation were either kept in room air (air-treated control) or exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery. RESULTS: In air-treated grafts, mRNA levels for interleukin-6, intracellular adhesion molecule-1, cyclooxygenase-2, and inducible nitric oxide synthase promptly increased. Sequential histopathologic analysis of untreated grafts revealed initial rapid epithelial loss, subsequent recruitment of inflammatory infiltrates, and local hemorrhage in the lamina propria, which extended downward to the epithelial crypt and muscle layer with time. CO effectively blocked proinflammatory cascade during I/R injury, inhibited upregulation of inflammatory molecules and ameliorated intestinal tissue injuries. Beneficial effects of CO were associated with improved graft blood flow without inhibiting endogenous HO-1 activity. Recipient animal survival was significantly improved with CO to 100% versus 58% in air-treated controls. CONCLUSIONS: These results indicate a significant role for CO in protecting the intestine from cold I/R injury associating with small intestinal transplantation.